The over-all objective of this proposal is to elucidate the role of estradiol in the stimulation of progesterone synthesis by the corpora lutea (CL) of pregnant rat and to determine whether LH and prolactin, of either pituitary or placental origin, act on the CL to provide the androgenic precursor for estradiol biosynthesis and to generate estradiol receptor, prerequisite for the luteotrophic effect of estradiol. The first approach, using radioimmunoassay, will be to determine whether estradiol is necessary for progesterone synthesis throughout pregnancy and whether estradiol stimulates pregesterone in a dose dependent manner. Using isolated corpora lutea in vitro and in vivo we will determine if the long acting role of LH in the "luteotrophic process" is to stimulate the synthesis of the androgenic precursor for estradiol biosynthesis and whether LH dependent corpora lutea are estradiol dependent. The possibility that prolactin stimulates the generation of cytoplasmic estradiol receptor will then be investigated using a radioreceptor technique. Whether placentas take over the regulation of luteal function by secreting the hormones (LH-like, and Prolactin-like from maternal and fetal placenta) which will induce estradiol formation in the corpora lutea and set the mechanism by which estradiol stimulates progesterone synthesis will be investigated. Rat placental luteotrophin will be measured in the placenta and serum of hypophysectomized rats by radioreceptor assay using corpora lutea membranes in order to determine whether rPL is secreted only until day 14 of pregnancy and whether the hormone, detectable around day 17, is mammotrophic and not luteotrophic. Finally, we will determine if the decline in progesterone synthesis from day 18 of pregnancy is related to the disappearance of rPL from day 14 and to the decline of estradiol receptor.